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Mental Illness May Be Teenie, Tiny Neurotransmitter Receptors Sightly Out of Alignment…

In a simplified and, somewhat metaphorical way, we can start to connect subjective experiences of harmful and disruptive clinical and mental health behaviors and micro events at the cellular and synaptic level.

Just putting together snippets from summary reports of a couple of recent studies we have the following:
“The fragmented self: imbalance between intrinsic and extrinsic self-networks in psychotic disorders”

From the papers Abstract:
“Self-disturbances are among the core features of schizophrenia and related psychotic disorders. The basic structure of the self could depend on the balance between intrinsic and extrinsic self-processing. We discuss studies on self-related processing in psychotic disorders that provide converging evidence for disrupted communication between neural networks subserving the so-called intrinsic self and extrinsic self. This disruption might be mainly caused by impaired integrity of key brain hubs.

The intrinsic self has been associated with cortical midline structures involved in self-referential processing, autobiographical memory, and emotional evaluation. Additionally, we highlight central aspects of the extrinsic self in its interaction with the environment using sensorimotor networks, including self-experience in sensation and actions. A deficient relationship between these self-aspects because of disrupted between-network interactions offers a framework to explain core clinical features of psychotic disorders. In particular, we show how relative isolation and reduced modularity of networks subserving intrinsic and extrinsic self-processing might trigger the emergence of hallucinations and delusions, and why patients with psychosis typically have difficulties with self–other relationships and do not recognise mental problems.”

“…nerve cells talk to one another across the small gaps between them, a process known as synaptic transmission (synapses are the connections between neurons). Information is carried from one cell to the other by neurotransmitters such as glutamate, dopamine, and serotonin, which activate receptors on the receiving neuron to convey excitatory or inhibitory messages. Synapses are very complicated molecular machines. They are also tiny: only a few millionths of an inch across. They have to be incredibly small, since we need a lot of them; the brain has around 100 trillion of them, and each is individually and precisely tuned to convey stronger or weaker signals between cells.

To visualize features on this sub-microscopic scale, the researchers turned to an innovative technology known as single-molecule imaging, which can locate and track the movement of individual protein molecules within the confines of a single synapse, even in living cells. Using this approach, the scientists identified an unexpected and precise pattern in the process of neurotransmission. The researchers looked at cultured rat synapses, which in terms of overall structure are very similar to human synapses.

“We are seeing things that have never been seen before. This is a totally new area of investigation…For many years, we’ve had a list of the many types of molecules that are found at synapses, but that didn’t get us very far in understanding how these molecules fit together, or how the process really works structurally…”

A new model of the molecular architecture at points of neuron-to-neuron contact in the brain, based on measuring the location of individual protein molecules at the sites where cell contact is made. Amazingly, proteins in the two cells align with each other to extremely high accuracy, suggesting a protein column spanning the two cells, and assuring that neurotransmitter release occurs with highest probability near the receptors that sense it. NeuroscienceNews.com image is credited to Jim Stanis.

In the paper, Blanpied describes an unexpected aspect to this architecture that may explain why synapses are so efficient, but also susceptible to disruption during disease: at each synapse, key proteins are organized very precisely across the gap between cells. “The neurons do a better job than we ever imagined of positioning the release of neurotransmitter molecules near their receptors,” Blanpied says. “The proteins in the two different neurons are aligned with incredible precision, almost forming a column stretching between the two cells.” This proximity optimizes the power of the transmission, and also suggests new ways that this transmission can be modified.

…if adhesion molecules are not placed correctly at the synapse, synapse architecture will be disrupted, and neurotransmitters won’t be able to do their jobs…in at least some disorders, the issue may be that even though the brain has the right amount of neurotransmitter, the synapses don’t transmit these molecules efficiently.”http://neurosciencenews.com/neurotransmission-neuroimaging-4744/